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Evaluation of l-1-[18F]Fluoroethyl-Tryptophan for PET Imaging of Cancer

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Abstract

Purpose

Fluorine-18 labeled tryptophan analog l-1-[18F]fluoroethyl-tryptophan (l-1-[18F]FETrp) was designed for positron emission tomography (PET) imaging of cancer by dual targeting of the overexpressed amino acid transporters and altered indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway of tryptophan metabolism. In our previous study, we described the radiosynthesis and preliminary evaluation of l-1-[18F]FETrp for PET imaging of breast cancer. The aim of this study was to investigate the in vivo imaging mechanism and further evaluate this radiotracer in more wide range types of cancers including prostate cancer, lung cancer, and glioma.

Procedures

The mice bearing subcutaneous PC-3 prostate cancer, subcutaneous H2009 and H460 lung cancers, subcutaneous MDA-MB-231, orthotopic A549 lung cancer, and intracranial 73C glioma were employed to evaluate l-1-[18F]FETrp for PET imaging of cancer. The in vivo catabolism of l-1-[18F]FETrp in the tumor was studied by analysis of PC-3 extracts with radio-HPLC.

Results

Small animal PET/CT imaging of l-1-[18F]FETrp visualized all tumors in these different mouse models with high accumulations of radioactivity in PC-3 (7.5 ± 0.6 % ID/g), H2009 (5.3 ± 0.8 % ID/g), H460 (9.0 ± 1.4 % ID/g), A549 (4.5 ± 0.5 % ID/g), and 73C (4.1 ± 0.7 % ID/g) tumors. The radio-HPLC analysis of PC-3 tumor extracts revealed that about 30 % of l-1-[18F]FETrp was converted into a highly polar radioactive metabolite. The uptake in H460 cancer was about 1.7-fold higher than that in H2009 cancer, which indicated l-1-[18F]FETrp could differentiate these subtypes of lung cancers (H2009 and H460) by imaging quantification. Furthermore, small animal PET/CT imaging in intracranial glioma revealed l-1-[18F]FETrp could pass blood-brain barrier (BBB) and accumulate in glioma with a favorable imaging contrast (tumor-to-brain 2.9).

Conclusions

l-1-[18F]FETrp highly accumulated in a wide range of malignancies including lung cancer, prostate cancer, and glioma. These results suggested that l-1-[18F]FETrp is a promising radiotracer for PET imaging of cancer.

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Acknowledgments

We are grateful to Prof. Xiankai Sun and Dr. Aditi Mulgaonkar in UTSW for providing scientific insights and experimental supports. We also would like to thank Robert Hallgren in UTSW for producing [18F]F− ion used in radiotracer synthesis.

Funding

This work was financially supported by the UT Southwestern Simmons Cancer Center Grant (NIH 5P30 CA 142543), the American Cancer Society and the Simmons Cancer Center (ACS-IRG-02-196), the UT Southwestern High Impact/High Risk funds, NINDS K99/R00 (R00NS073735), the Jonesville Foundation and CRI start-up funds to W.P.G.

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Authors and Affiliations

  1. Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Yangchun Xin, Li Liu & Hancheng Cai

  2. Katzin Diagnostic & Research PET/MR Center, Nemours/Alfred I. DuPont Hospital for Children, Wilmington, DE, 19803, USA

    Yangchun Xin

  3. Children’s Research Institute, Department of Pediatrics, Neuroscience, Neurology & Neurotherapeutics, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Xiaofei Gao & Woo-Ping Ge

  4. Department of Radiology, Mayo Clinic, Jacksonville, FL, 32224, USA

    Manoj K. Jain & Hancheng Cai

  5. Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Hancheng Cai

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  1. Yangchun Xin
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Correspondence to Hancheng Cai.

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Xin, Y., Gao, X., Liu, L. et al. Evaluation of l-1-[18F]Fluoroethyl-Tryptophan for PET Imaging of Cancer. Mol Imaging Biol 21, 1138–1146 (2019). https://doi.org/10.1007/s11307-019-01327-4

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